The Baeyer-Villiger oxidation of ketones to esters (or...

The Baeyer-Villiger oxidation of ketones to esters (or lactones) occurs by the following mechanism:
For endo-substituted bicyclo[2.2.1]heptan-7-ones, the product ratios shown below are observed. Account for the effect of the substituents.

Key Concepts

Substituent Effects in Reaction Mechanisms

Substituent effects pertain to how attached groups influence the course and outcome of a reaction through their electronic and steric properties. In oxidation reactions like the Baeyer-Villiger, substituents can either stabilize or destabilize intermediates or transition states, thereby altering reaction rates and selectivity. Electron-donating groups can facilitate migration by stabilizing positive character, while bulky groups might impose steric hindrance, changing the preferred migration pathway.

Baeyer-Villiger Reaction Mechanism

The Baeyer-Villiger oxidation transforms ketones into esters or lactones through a two-step process: initially, a nucleophilic attack by a peracid on the carbonyl group forms a tetrahedral (Criegee) intermediate, which then undergoes a rearrangement where an alkyl or aryl group migrates to an adjacent oxygen atom. This oxygen insertion is the defining feature of the reaction and determines the formation of the final product.

Migratory Aptitude

Migratory aptitude is the tendency of different substituents attached to the carbonyl carbon to shift during the rearrangement step. This aptitude is influenced by the ability of the migrating group to stabilize positive charge and its steric environment. Groups that are more electron-rich or better able to accommodate developing positive charge tend to migrate more readily, affecting the overall selectivity of the reaction.

Stereoelectronic Effects

Stereoelectronic effects describe how the spatial arrangement of orbitals affects chemical reactivity. In the context of the Baeyer-Villiger oxidation, the orientation of substituents relative to the reacting carbonyl is crucial; groups positioned favorably (e.g., in an endo configuration) can have enhanced or diminished migration tendencies based on their ability to interact with the developing charges in the transition state. This spatial relationship helps explain differences in product ratios observed in empirical studies.

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